Furanocoumarins are naturally occurring plant metabolites that are extremely toxic because they react with pyrimidine bases in DNA and with general cellular proteins when photoactivated and because they interact reversibly and irreversibly with P450 catalytic sites. These photobiologic properties of furanocoumarins have been exploited for the treatment of a variety of human skin diseases even though the mechanisms for their metabolism and their effects on endogenous drug metabolizing P450s have not been well established. Much can be learned about their metabolism and mechanism of P450 inhibition by studying the P450s that are in herbivorous insects specialized to feed on host plants containing high levels of liner and angular forms of these furanocoumarins.